突变的识别与peroxisome-to-mitochondrion mistargeting丙氨酸/乙醛酸转氨酶在初级hyperoxaluria 1型。
文章的细节
-
引用
复制到剪贴板 -
普渡大学体育,高田Y, Danpure CJ
突变的识别与peroxisome-to-mitochondrion mistargeting丙氨酸/乙醛酸转氨酶在初级hyperoxaluria 1型。
J细胞杂志。1990年12月,111 (6 Pt (1): 2341 - 51。
- PubMed ID
-
1703535 (在PubMed]
- 文摘
-
之前我们已经表明,在一些患者主要hyperoxaluria 1型(PH1),疾病与mistargeting通常酶酶丙氨酸/乙醛酸转氨酶(AGT)线粒体(C.J. DanpureP.J.库珀,P.J.明智和公关詹宁斯。j .细胞生物108:1345 - 1352)。合成、放大、克隆和测序AGT cDNA从PH1患者线粒体AGT (mAGT)。这个确定了三个点突变导致氨基酸替换预测AGT蛋白序列。用PCR和allele-specific寡核苷酸杂交,一系列PH1病人和控制这些突变筛查。这表明所有八个PH1 mAGT患者携带至少一个相同的三个突变的等位基因。两人为这等位基因纯合,六人杂合的。在至少三个杂合的,看来只有突变等位基因表达。所有三个突变从PH1患者缺乏mAGT缺席。突变编码一个g - - - - - Arg替换170残渣中没有任何个人的控制。 However, the other two mutations, encoding Pro----Leu and Ile----Met substitutions at residues 11 and 340, respectively, cosegregated in the normal population at an allelic frequency of 5-10%. In an individual homozygous for this allele (substitutions at residues 11 and 340) only a small proportion of AGT appeared to be rerouted to mitochondria. It is suggested that the substitution at residue 11 generates an amphiphilic alpha-helix with characteristics similar to recognized mitochondrial targeting sequences, the full functional expression of which is dependent upon coexpression of the substitution at residue 170, which may induce defective peroxisomal import.